This proposal seeks support for our continuing studies on the chemistry and biochemistry of novel nucleosides, in particular 7-methylguanosine. We have found that 7-methylguanosine, a naturally occuring nucleoside in mRNAs and tRNAs, has a unique chemistry which may play a role in its unique regulatory function in nucleic acids. Our objectives in this research are: a) a study of the chemistry of 7-methylguanosine, in particular its reaction with gamma-ketoaldehydes and related compounds and its unique redox chemistry; b) applications of these reactions as probes for 7-methylguanosine function in RNAs and the determination of any biological relevance of these interactions; c) a detailed study of the interaction of 7-methylguanosine cap structures with purified initiation factors using chemical and spectroscopic techniques; and d) the investigation of 7-methylguanosine-specific reactions as possible potentiators of the action of alkylating agents in DNA base-pairing processes and degradative mechanisms and might have implications in combination chemotherapy. 7-Methylguanosine appears to play a critical role in the regulator processes of a variety of transfer- and messenger-RNAs. Our recent findings suggest that certain compounds, such as gamma-ketoaldehydes may exert their inhibitory effect by a facile reaction with the 7-methylguanosine cap structure. In addition, the redox chemistry of 7-methylguanosine may have some biological relevance. By investigating 7-methylguanosine in terms of its chemistry and biochemistry, we hope to gain a better understanding of the function of this unusual nucleoside.